CD4+ T-cell, CD8+ T-cell, CD4+ /CD8+ ratio, and apoptosis as a response to induction phase chemotherapy in pediatric acute lymphoblastic leukemia

Main Article Content

May Fanny Tanzilia
Andi Cahyadi
Yetti Hermaningsih
Endang Retnowati
I Dewa Gede Ugrasena

Abstract

Background Acute lymphoblastic leukemia (ALL) is a neoplastic disease resulting from somatic mutation in the lymphoid progenitor cells, often occuring in children aged 2-5 years, predominantly in males. Results from the induction phase of chemtherapy are used to measure success, but the failure remission rate is still high. Increased apoptosis of cancer cells, as induced by CD4+ and CD8+T-cells, is an indicator of prognosis and response to chemotherapy.

Objective To assess for correlations between CD4+, CD8+, or CD4+/CD8+ ratio to the chemotherapy induction phase response (i.e., apoptosis) in pediatric ALL patients.

Methods This observational analytical cohort study was done in 25 pediatric ALL patients. Whole blood (3 mL) with EDTA anticoagulant were used to measure absolute counts of CD4+, CD8+, and CD4+/CD8+ ratio. Peripheral blood mononuclear cells (PBMC) were examined for apoptosis. The principle of CD4+, CD8+ examination was bond between antigens on the surface of the leukocyte in the blood with fluorochrome labeled antibodies in the reagents, while the principle of apoptosis examination was FITC Annexin V will bonds with phosphatidylserine that moves out of the cell when the cell undergoes apoptosis, then intercalation with propidium iodide (PI). All examination were detected by flow cytometry BD FACSCalibur.

Results Subjects were 25 newly-diagnosed, pediatric ALL patients (64% males and 36% females). Most subjects were 3 years of age (20%). Numbers of CD4+ and CD8+ cells, as well as CD4+/CD8+ were significantly decreased after chemotherapy. However, apoptosis was not significantly different before and after chemotherapy (P=0.689), There were significant negative correlations between apoptosis and CD4+ (P=0.002; rs=-0.584), and CD8+ (rs=-0.556; P=0.004), before chemotherapy. In addition, CD4+-delta and apoptosis-delta also had a significant positive correlation (rs=0.478; P=0.016). However, no correlation was found between the CD4+/CD8+ ratio and apoptosis, before or after chemotherapy.

Conclusion There are significantly lower mean CD4+, CD8+, and CD4+/CD8+ ratio after chemotherapy than before. Also, there are significant correlations between CD4+-delta and apoptosis-delta, as well as between apoptosis and CD4+, CD8+, and CD4+/CD8+, before chemotherapy. CD4+, CD8+, and CD4+/CD8+ can be used to predict apoptosis before chemotherapy. In addition, CD4+-delta can be used to predict apoptosis-delta as a response to induction phase chemotherapy in pediatric ALL.

Article Details

How to Cite
1.
Tanzilia M, Cahyadi A, Hermaningsih Y, Retnowati E, Ugrasena ID. CD4+ T-cell, CD8+ T-cell, CD4+ /CD8+ ratio, and apoptosis as a response to induction phase chemotherapy in pediatric acute lymphoblastic leukemia. PI [Internet]. 22Jun.2017 [cited 22Apr.2021];57(3):138-4. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/1307
Section
Articles
Received 2017-03-03
Accepted 2017-06-12
Published 2017-06-22

References

1. Pui CH. Acute lymphoblastic leukemia. In: Williams Hematology. Kenneth Kaushansky, Marshall A Lichtman, Ernest Beutler, et al., editors. 8th ed. New York The McGraw-Hill Companies, Inc.; 2010. p. 1409-30.
2. Wintrobe, MW. Acute lymphoblastic leukemia in children. In: Wintrobe’s Clinical Hematology. John P Greer, Daniel A Arber, Bertil Glader, et al., editors. 10th ed. Philadelphia: Lippincott Williams and Wilkins; 2009. p. 2209-60.
3. Stankovic T, Marston E. Molecular mechanisms involved in chemoresistance in paediatric acute lymphoblastic leukaemia. Srp Arh Celok Lek. 2008;136:187-92.
4. Liang DC, Pui CH. Childhood acute lymphoblatic leukaemia. In: Postgraduate Hematology. A. Victor Hoffbrand, Daniel Catovsky, Edward GD Tuddenham, editors. 5th ed. Ljubljana: Blackwell Publishing; 2008; p. 542-7.
5. Permono B. Leukemia akut. Buku ajar hematologi onkologi anak. Jakarta: Badan Penerbit IDAI; 2010. p.236-47.
6. Simanjorang C, Kodim N, Tehuteru E. Perbedaan kesintasan 5 tahun pasien leukemia limfoblastik lkut dan mieloblastik akut pada anak di rumah sakit kanker “Dharmais”. Indonesian J Cancer. 2013;7:15-21.
7. Oluboyo AO, Meludu SC, Onyenekwe CC, Oluboyo BO, Chianakwanam GU, Emegakor C. Assessment of immune stability in breast cancer subjects. Eur Sci J. 2014;10:224-8.
8. Kresno SB. Ilmu dasar onkologi. 2nd ed. Jakarta: Fakultas Kedokteran Universitas Indonesia; 2011. p. 156-283.
9. Wong RS. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res. 2011;30:87.
10. Elzubeir AM, Angi AM, Rahoum HM, Osama A. Prognostic significance of immune function parameters (CD4, CD8 and CD4/CD8 ratio) in Sudanese patients with chronic lymphocytic leukemia. Int J Multidisciplinary Curr Res. 2016;4:650-3.
11. Technical Data Sheet BD Multitest CD3 FITC/ CD8 PE/ CD45 PerCP/ CD4 APC Reagent, BD Pharmingen 2012.
12. Technical Data Sheet FITC Annexin V Apoptosis Detection Kit I, BD Pharmingen 2008.
13. Nguyen VT, Melville A, Nath S, Story C, Howell S, Sutton R, et al. Bone marrow recovery by morphometry during induction chemotherapy for acute lymphoblastic leukemia in children. PLoS One. 2015;10:1-10.
14. Verma R, Foster RE, Horgan K, Mounsey K, Nixon H, Smalle N, et al. Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer. Breast Cancer Res. 2016;18:10.
15. Salem MP, El-Shanshory MR, El-Desouki NI, Abdou SH, Attia MA, Zidan AA, et al. Children with acute lymphoblastic leukemia show high numbers of CD4+ and CD8+ T-cells which are reduced by conventional chemotherapy. Clin Cancer Investig J. 2015;4:603-9.
16. Wu CP, Qing X, Wu CY, Zhu H, Zhou HY. Immunophenotype and increased presence of CD4(+)CD25(+) regulatory T cells in patients with acute lymphoblastic leukemia. Oncol Lett. 2012;3:421-4.
17. Laane E, Panaretakis T, Pokrovskaja K, Buentke E, Corcoran M, Soderjall S, et al. Dexamethasone–induced apoptosis in acute lymphoblastic leukemia involves differential regulation of Bcl-2 family members. Haematologica. 2007;92:1460-9.
18. Liu T, Raetz E, Moos PJ, Perkins SL, Bruggers CS, Smith F, et al. Diversity of the apoptotic response to chemotherapy in childhood leukemia. Leukemia. 2002;16:223-32.
19. Blagosklonny MV. Cell death beyond apoptosis. Leukemia. 2000;14:1502-8.
20. Niknafs B. Induction of apoptosis and non-apoptosis in human breast cancer cell line (MCF-7) by cisplatin and caffeine. Iran Biomed J. 2011;15;130-3.
21. Dewyer NA, Wolf GT, Light E, Worden F, Urba S, Eisbruch A, et al. Circulating CD4-positive lymphocyte levels as predictor of response to induction chemotherapy in patients with advanced laryngeal cancer. Head Neck. 2014;36:9-14.